Cocrystals of quercetin: synthesis, characterization, and screening of biological activity

Cocrystallization of quercetin with 22 cocrystal formers, i.e. phenolic acids, proline, urea, N -acetylcytosine, carnitine, dacarbazine, diflunisal, kojic acid, lactamide, baclofen, pyrazole, edaravone, salicylamide, O -acetylsalicylamide, 2-imidazolidinone, allopurinol, dipyridamole, 5-sulfosalicylic acid, and 4-sulfobenzoic acid resulted in cocrystals with various stoichiometric ratios. The cocrystals were characterized by FT-IR, DSC, and XRPD. Some of them were non-hygroscopic and stable to thermal stress. The cocrystals quercetin:pyrazole (1:1), quercetin:imidazolidinone (1:1), and quercetin:baclofen (1:2) were found to be stable at various relative humidity conditions at 20–40 °C for up to 3 months. The in vitro antioxidant activity, cytotoxicity, and serine protease inhibitory activity were tested. The best inhibitory activity to pathophysiological proteases was observed for cocrystals with N -acetylcytosine, carnitine, and kojic acid; these cocrystals were the most potent inhibitors of thrombin. About two times better cytotoxic activity to human cervical cancer cells (HeLa) and human colon cancer cells (Caco-2) in comparison with quercetin itself was observed for quercetin:kojic acid (2:1). Graphical abstract